The present invention relates to a crystallization apparatus and a crystallization method. More specifically, the present invention relates to a crystallization apparatus which enables an induction time for crystallization to be shorter, and can provide large crystals with a narrow size distribution, as well as to a method for obtaining such crystals. Furthermore, the present invention relates to a method for controlling crystal polymorphism.
One known method for crystallization is to raise the concentration of the solution by evaporating the solvent. In this method, when the concentration of the material to be crystallized in the solution increases, the evaporation rate of the solvent decreases, so that there is a disadvantage that the crystallization gradually slows down, and the distribution of the diameters of the obtained crystals becomes broad. Furthermore, there is a problem with regard to costs, because the solvent has to be evaporated over a long period of time.
On the other hand, there is also a crystallization method, that is cooling crystallization. However, there are many problems such as: the crystallization requires a lot of time; separation is difficult; and an adjustment of the particle size is difficult. Moreover, there is a problem that the cooling is expensive.
Furthermore, a substance can take various crystal forms, such as xcex1-crystals, xcex2-crystals, and xcex3-crystals, and the solubility of the substance varies depending on the crystal form. Especially in the field of medicine, it is important to make a crystal form uniform, since uniform solubility of the pharmaceuticals can be obtained by a specified crystal form. However, it is difficult to attain a specified crystal form (that is, to control crystal polymorphism), and it is also difficult to separate crystals with a specified crystal form from a mixture of crystals with various crystal forms.
Consequently, there is a demand for a fast and simple method for obtaining crystals with uniform crystal form (that is, possible to control crystal polymorphism), narrow size distribution and large diameters.
A crystallization apparatus in accordance with the present invention includes an agitation tank, a liquid circulation means for circulating a liquid or a slurry along a wall of the agitation tank, and one or more temperature difference creation means capable of creating a temperature difference at the wall of the agitation tank, wherein the temperature difference creation means is installed to the agitation tank.
Another crystallization apparatus in accordance with the present invention includes an agitation tank provided with a liquid spouting device made of a rotation shaft and one or more liquid feeding means mounted to the rotation shaft, and one or more temperature difference creation means capable of creating a temperature difference at a wall of the agitation tank.
In a preferable embodiment, the temperature difference creation means is one or more heating means or cooling means.
In a preferable embodiment, the temperature difference creation means is a heating means, which is provided at a region where liquid or slurry spouted by rotating the liquid spouting device contacts the wall of the agitation tank or a region below that region, and which increases the temperature of the spouted liquid or slurry above the temperature of surrounding liquid or slurry.
In another preferable embodiment, the temperature difference creation means is a cooling means, which is provided at a region where liquid or slurry spouted by rotating the liquid spouting device contacts the wall of the agitation tank or a region below that region, and which decreases the temperature of the spouted liquid or slurry above the temperature of surrounding liquid or slurry.
In a preferable embodiment, the temperature difference creation means includes two cooling means and one heating means, the heating means is arranged below the two cooling means, and a liquid or slurry is spouted against a portion between the two cooling means or against a portion of the lower cooling means by rotating the liquid spouting device.
In another preferable embodiment, the liquid feeding means is a gutter-shaped body, a pipe body, a plate-shaped body, or a conically shaped hollow truncated corn body.
In a preferable embodiment, the crystallization apparatus is a cooling crystallization apparatus.
In another preferable embodiment, the crystallization apparatus is a concentration crystallization apparatus.
A method for controlling crystal polymorphism in accordance with the present invention comprises concentrating a liquid for generating crystals while circulating the liquid along a tank wall provided with a temperature difference.
Another method for controlling crystal polymorphism comprises spouting a liquid or a slurry from a liquid spouting device containing a rotation shaft and one or more liquid feeding means mounted to the rotation shaft, and contacting the spouted liquid or slurry with a tank wall whose temperature is different from the temperature of the liquid or slurry and circulating the liquid or slurry.
In a preferable embodiment, the spouted liquid or slurry is contacted with a tank wall whose temperature is higher than the temperature of the liquid or slurry.
In another preferable embodiment, the spouted liquid or slurry is contacted with a tank wall whose temperature is lower than the temperature of the liquid or slurry.
A method for growing crystals with large average diameter in accordance with the present invention comprises spouting a liquid or a slurry from a liquid spouting device containing a rotation shaft and one or more liquid feeding means mounted to the rotation shaft, and contacting the spouted liquid or slurry with a tank wall whose temperature is different from the temperature of the liquid or slurry and circulating the liquid or slurry.